As a young director in the early 1960s, Isaiah became interested in the work of the avant-garde Belgian playwright Michel de Ghelderode. He directed the American premiere of Ghelderode’s farce Pantagleize and several other works by the playwright, including Barabbas and The Women at the Tomb.

During this same period, Isaiah directed a production of German playwright Bertolt Brecht’s The Exception and the Rule, in an English translation by Eric Bentley. The play was well receivedand Isaiah’s collaboration and friendship with his neighbor Eric Bentley continued for several decades, with the two directing the first of the many political cabarets that Isaiah would be involved in.

Having begun his theatrical life in the Yiddish theatre, Isaiah continued to direct plays with Jewish themes, including the world premiere of Isaac Bashevis Singer’s Shlemiel the First in 1974, an early example of his long association with that writer. Other Jewish- and Yiddish-themed shows under Isaiah’s direction were The Theatre of Peretz, an adaptation of the stories of I. L. Peretz (“The Father of Modern Yiddish Literature”) that Isaiah also wrote and acted in and that enjoyed a long off-Broadway run; a play about Jewish immigrants called Children in a New Land; a show based on the works of Singer, Peretz, and Kobrin called Bird, Beast, & Dybbuk (by Mike Kellin); and the Yiddish music revue On Second Avenue.

Isaiah’s theatrical interests were varied and not limited to Jewish themes, however, and his directing career during the 1970s and '80s encompassed many genres. In 1973 he directed Leslie Weiner’s play An Evening with the Poet Senator (with Tandy Cronyn and Henderson Forsythe) and, in 1977, the first run of comedian Steve Allen’s semi-autobiographical drama, The Wake, with a young Anthony Michael Hall making his stage debut playing Allen as a boy.

Isaiah’s long-abiding love of Shakespeare’s sonnets was reflected in his staging of Dialogue for Lovers, Eve Merriam’s dramatic adaption of Shakespeare’s sonnets (with Fritz Weaver and Estelle Parsons), and his fascination with classical ballet drew him to Richard Crane’s play about the Ballets Russes, Clownmaker, which he directed with Jerome Dempsey as Diaghilev and a young Stephen Lang as Nijinsky. (The play opened at the White Barn Theatre in Connecticut in 1976 and then at the Wonderhorse Theatre in New York City in 1982.) Always interested in Irish literature, Isaiah directed a production of Sean O’Casey’s The Shadow of Gunman at Symphony Space in 1979 and, that same year, worked with the New York Lyric Opera to direct the New York premiere of The Plough and the Stars, Elie Siegmeister’s opera based on O'Casey’s play of that name. In 1986, Isaiah directed Susie Burke’s play about the poet Yeats’s relationship with activist Maud Gonne, Cauldron, at the Irish Arts Center in New York.